A. Gregory Matera

A. Gregory Matera

RNA Processing: Biogenesis of Small Ribonucleoproteins in Health and Disease

Telephone: (919) 962-2770

FAX: (919) 962-8472

E-mail: agmateraemail.unc.edu

Office: 415 Fordham Hall

Mailing Address:
CB# 3280, Coker Hall
The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina 27599-3280

Professor (Initial Appointment 2007)
Ph.D. University of California at Davis (1990)
B.A. University of Colorado at Boulder (1984)

Matera Lab Homepage Selected Publications

Research at a Glance

Genetics and Cell Biology of RNP assembly and transport
Developmental regulation of Protein Arginine Methylation
Drosophila and mouse models of Spinal Muscular Atrophy

Synopsis
We use three different model systems (mouse, human and fruitfly) to study the molecular, cellular and developmental biology of small nuclear ribonucleoproteins (snRNPs). Why are snRNPs so interesting?

Without snRNPs, pre-mRNA splicing (and thus eukaryotic life) would not be possible.
The biogenesis of snRNPs is a paradigm for assembly of other factors, such as micro RNPs.
A reduced capacity for snRNP biogenesis is associated with a neurogenetic disease called Spinal Muscular Atrophy

Introduction
Small nuclear ribonucleoproteins (snRNPs; pronounced ‘snurps’) are required for pre-messenger RNA splicing and are thus essential components of all eukaryotic cells. Whereas the basic mechanics of splicing are fairly well-understood, the biogenesis of snRNPs is relatively unclear. The long-term goal of our laboratory is to understand the molecular mechanisms that govern the assembly and subcellular localization of small RNPs. In short, we seek to uncover the process by which snRNPs are packaged, transported and delivered to their nuclear sites of action. Curiously, the initial phases of snRNP biogenesis actually begin in the cytoplasm, following nuclear export of the pre-snRNA transcript. Assembly into stable RNP particles is mediated by the Survival Motor Neurons (SMN) protein complex. Subsequently, these small RNPs are imported back into the nucleus. Defects in the assembly of Sm-class small RNPs are associated with a neurodegenerative disorder called Spinal Muscular Atrophy (SMA). Patients with SMA typically die in childhood. Although snRNP biogenesis is compromised in patient-derived cells, the underlying cause of the SMA phenotype is not fully understood. Plausibly, mutations in other snRNP biogenesis genes may phenocopy SMA. Thus a detailed understanding of snRNP metabolism is essential not only to the study of RNA processing, but will also be important in developing treatments for neuromuscular disease. To gain insight into the biogenesis of snRNPs and its role in the pathogenesis of SMA, we have developed models in Drosophila and mammalian systems to study small RNP trafficking and assembly.